1. Technical Field
The present disclosure relates to adhesive modalities for repair of biological tissues.
2. Related Art
Medical adhesives or “tissue glue” have much potential in medicine. Certain adhesive materials are known which may be used to adhere tissue such as skin. For example, cyanoacrylate adhesives been used to bond tissue. In addition to cyanoacrylate adhesives, other types of materials have been reported to adhere to skin. For example, U.S. Pat. No. 4,839,345 to Doi et al. reports a hydrated crosslinked protein adhesive gel that is used as a cataplasm or cosmetic mask that will externally adhere to skin but can be removed and then re-adhered to the skin. Other crosslinked protein hydrogels have been reported to serve as a proteinaceous substrate to deliver therapeutic agents such as enzymes or drugs through skin or mucous membranes. Still other materials have been used as hemostatic agents to stop or prevent bleeding. For example, mixtures of fibrinogen and thrombin such as TISSEEL® sealant available from Baxter International, Inc. or BERIPLAST-P® hemostatic agent or sealant available from Aventis Behring, have been used in vascular surgery to seal tissue such as blood vessels and thus prevent blood leakage. However, surgical adhesives can tend to form a physical barrier between the item or items being attached to biological tissue, thus interfering with tissue ingrowth into the item when ingrowth is desired.
The use of medical gels such as hydrogels can be advantageous due to the physico-chemical properties of the hydrogels. Hydrogels typically have excellent compatibility with human and animal tissue. Physically cross linked hydrogels can withstand attack by body fluids, blood, urine and other bodily secretions without significant damage. Many are typically non-adherent to tissue, do not have an affinity for binding to proteins and do not have cell adsorption. Hydrogels are typically non-thrombogenic. These characteristics have been utilized, e.g., for prevention of adhesions after surgery. The ability of hydrogels to act as bulking agents has been utilized in connection with treatment of gastroesophageal reflux disease (GERD), urinary incontinence, fecal incontinence and sterilization of mammals. Hydrogels have also been used to create a matrix in the treatment of damaged cartilage.
Click chemistry is a popular term for reliable reactions that make it possible for certain chemical building blocks to “click” together and form an irreversible linkage. See, e.g., US Pub. No. 2005/0222427. In the case of azide-alkyne click chemistry, the reactions may be catalyzed or uncatalyzed. For example, copper-free click chemistry was recently developed by Bertozzi and colleagues using difluorinated cyclooctyne or DIFO, that reacts with azides rapidly at physiological temperatures without the need for a toxic catalyst. See, e.g., Baskin et al., Copper Free Click Chemistry for Dynamic In Vivo Imaging, PNAS, vol. 104, no. 43, 16793-16797 (Oct. 23, 2007). The critical reagent, a substituted cyclooctyne, possesses ring strain and electron-withdrawing fluorine substituents that together promote a [3+2] dipolar cycloaddition with azides. See also, US Pub. No. 2006/0110782 and Codelli et al., Second Generation Difluorinated Cyclooctynes for Copper-Free Click Chemistry, J. Am. Chem. Soc., vol. 130, no. 34, 11486-11493 (2008). Another suitable cyclooctyne is 6,7-dimethoxyazacyclooct-4-yne (DIMAC). See, Sletton and Bertozzi, A hydrophilic azacyclooctyne for Cu-free click chemistry, Org. Lett. (2008) 10 (14), 3097-3099. Other click chemistry reactions include Diels-Alder reactions, thiol-alkene reactions, and maleimide-thiol reactions.
It would be advantageous to be able to secure medical gels via selective attachment at target sites within the body to prevent migration of the hydrogel without interfering with other hydrogel properties such as durability and the ability to be generally non-adherent when or where desired.